"When a thing ceases to be a subject of controversy, it ceases to be a subject of interest. " WILLIAM HAZLITT (1778-1830) This is the fourth volume in a series which we started in 1997. In 1976, Varco and Delaney edited a "surgical bestseller" entitled Controversy in Surgery. This was fol lowed by a second volume in 1985. The immense success of these books among both surgical trainees and experienced surgeons, and their wide international ap peal, supported the editors' notion that a view of controversy is integral to teach ing. However, despite major advances in surgical science and practice, no other similar publication has since been put together with the objective of addressing major controversies in surgery. The aim of this series is to address such deficiency by covering the most crucial current controversies in general, vascular and trauma surgery. Since almost everything is controversial in surgery, we will be able to tackle different issues almost each year. The editors have selected a nationally/internationally recognized authority for each topic. Most books available today are either "North American: ' "British-Com monwealth" or "British-European: ' contributing to the constant transatlantic rival ry. Our series specifically aims to bridge this "culture gap" and includes North American, British, European, and other authors while maintaining a cohesive structure. This will hopefully also broaden the appeal of such a book across both sides of the Atlantic and beyond."

This book is divided into two main sections, and covers a broad range of issues important for health practitioners to be aware of when caring for people with co-morbid diabetes and depression. Section One of the book contains the overall ideas and the more recent developments in measuring psychological morbidity in people with diabetes. When attempting to identify people with depression or other psychological problems, it is important for practitioners to recognize the limitations of screening as well as its utility. Issues such as the basic principles regarding when and when not to screen, the cultural applicability of tools, different questionnaire formats and key concepts such as sensitivity and specificity of tools, and their positive and negative predictive value, will be considered. In particular there has been increased interest in the concept of diabetes-related distress and several tools have been developed to measure this. There are broad-based measures of distress such as the Problem Areas in Diabetes (PAID) scale, the Diabetes Adjustment Scale (DAS), The Diabetes Health Profile, The Fear of Hypoglycemia Scale, etc. There are also a range of generic quality of life tools which have been used effectively in people with diabetes; for example the Medical Outcomes Survey Short-Forms (SF36, SF12), the World Health Organisation Well-being questionnaire (WHO-5) and the EQ5-D. These tools are important because they measure aspects of psychological well-being that are specifically associated with the experience of having a long-term conditions and so have important implications for both self-care and health care practice. The potential overlap of symptoms of depression and symptoms of diabetes-related distress are considered in this section and the implications for practice discussed. Section Two covers the most commonly used tools that have been used to screen for depression. For each tool considered some information which is easily referred to by the readeris set out in a table which includes details of the authors, time of first use, country where it was first developed, some examples of the questions used, the languages it is available in, data on sensitivity/specificity. Each instrument will then be discussed in terms of its use in research as well as practice, and its applicability in different patient groups, different cultural settings and so on. Guidance on the practical use of each tool is included, and the most popular depression screening tools are focussed on.

This book represents the proceedings from a conference that took place in Dallas in the spring of 1999 which was entitled "Pediatric Gender Assignment - A Critical Reappraisal". Some participants rightfully argued that the conference really focused on the issue of pediatric gender assignment, and that reassignment was not applied in most cases. Their comments were reflected in the title of this monograph. This multidisciplinary meeting was sponsored by a conference grant from the National Institutes of Health, and a broad inquiry into this complex topic took place from many points of view. Basic scientists offered insight into mechanisms of sexual differentiation of the gonads, physical phenotype and imprinting of the central nervous system. Endocrinologists reviewed their experience in diagnosis and management, surgeons described traditional as well as innovative approaches, and there was strong representation from the ethical and behavioral sciences. In putting together such a panel, it was essential that we identify a cast of speakers who could address their viewpoints with strong convictions, and yet not let their passions render the meeting counter productive. We were not disappointed. While many differing points of view were firmly expressed by the panelists and audience, all viewpoints were accorded the respect they deserved. The concept behind the meeting and this book really originated in 1997 shortly after Diamond and Sigmundson published their long term follow up study of the John/Joan case.

Stephen P. Ethier and a panel of leading investigators comprehensively analyze the cellular, molecular, and endocrine factors in the development of cancers of the breast, prostate, endometrium, and ovary. Concentrating on defining the most important unresolved issues in the field, the authors review how steroid hormones function to regulate normal mammary gland homeostasis in humans, with particular emphasis on the roles of estrogen, progesterone, and growth factors. Comprehensive and up-to-date, Endocrine Oncology offers both basic and clinical researchers not only the latest molecular and cellular findings on endocrine cancers, but also a powerful critical analysis that will prove invaluable to all endocrinologists and oncologists working in the area today.

Ghrelin is a 28-amino acid acylated peptide predominantly produced by the stomach. It displays strong GH-releasing activity mediated by the hypothalamus-pituitary GH secretagogue (GHS)-receptors specific for synthetic GHS. Ghrelin also acts on other central and peripheral receptors and enables other actions including: stimulation of lactotroph and corticotroph secretion; food-intake; gastro-entero-pancreatic functions; metabolic; cardiovascular activity; and anti-proliferative effects. This volume aims to highlight the impact and function of the hormone ghrelin and provide insight to neuroendocrinologies and researchers interested in its molecular and clinical relevance.

Autoimmunity is the most common cause of endocrine disorders. This volume provides an up-to-date summary of recent advances in this important field. In addition, it describes developments in our understanding of conditions such as vitiligo and pernicious anaemia which are frequently associated with autoimmune endocrinopathies. There is a detailed review of animal models of endocrine disease which have contributed greatly to current knowledge. Furthermore, the aetiology, pathogenesis and treatment of the clinical disorders are discussed in depth. The book will be of interest to anyone working in the areas of endocrinology and immunology.

This book tells the story of diabetes, from ancient times to today, and provides an accessible introduction to the cause, treatment, and impact of the disease.Diseases have a history, and understanding that history helps us understand how best to treat and control disease today. Today's students are confronted with a panoply of often-frightening illnesses and afflictions - the Biographies of Disease series provides necessary information to understand the origin of various maladies, how they impact contemporary society, and how doctors and researchers from around the world are fighting to devise treatments to alleviate or cure these diseases.This volume, Diabetes, covers a disease that has been a common affliction from the beginning of recorded history, but has been increasing in its impact because of changes in diet and exercise, especially among the young. Diabetes examines all aspects of this disease, including: the diagnosis and treatment of diabetes from the ancient period to the present day; the definition of the various types of diabetes, and the role of glucose and insulin; diagnosis and treatment, with an emphasis on prevention for those at risk; the cultural impact of the disease - on individuals, on families, and on the economy; and, the state of current research on new forms of insulin, blood glucose meters, transplants, and weight control.The volume includes a glossary of important terms and a bibliography of accessible works that discuss the disease.

The rapid developments in molecular genetics have clarified many of the muta tions in monogenic thyroid diseases over the last two decades; now the target of molecular thyroid genetics has become the oligogenic thyroid diseases. These include the autoimmune thyroid diseases and familial thyroid cancers, both of which are much commoner than the monogenic diseases. However, the method ological approach to the genetics of these more complex diseases is still far from being well established. Although the discovery of susceptibility genes has been partially accomplished in complex diseases such as asthma, Crohn's dis ease, and types I and II diabetes mellitus, the elucidation of susceptibility genes in complex diseases remains a major challenge. This volume contains papers presented at the International Symposium on the Genetics of Complex Thyroid Diseases. This meeting was held in association with the International Thyroid Congress in Kyoto in October 2000 and sup ported in part by the Japan Intractable Diseases Research Foundation and Knoll Pharmaceuticals Inc. The symposium was the first international symposium con cerning the genetics of complex thyroid diseases and was restricted to the study of the autoimmune thyroid diseases and familial thyroid cancer. Twenty distin guished researchers from the United States, the United Kingdom, France, Ger many, Italy, and Japan were invited. Each presentation precipitated intense dis cussion and there was much consensus during the meeting. Nevertheless, this volume will leave the reader with a clear understanding of how little we still know.

This book includes the most significant contributions of the First International Symposium on "Multiple risk factors in cardiovascular disease", chaired by Professors A. V. Chobanian (Boston), A. M. Gotto Jr. (Houston), c. Lenfant (Bethesda), R. Paoletti and A. Zanchetti (Milan), held in Washington DC, 10-12 December 1990, which focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological evidence that individuals from industrialized countries often possess two or more risk factors which synergically increase the global risk profile. The evidence that isolated vascular risk factors are not commonly found in high risk patients but more often a combination of risk factors are detected, is highlighted. Many recent epidemiological data identifying the intrinsic and environ mental factors contributing to the development of atherosclerosis are discussed. These results, in parallel to basic and clinical research, underline how atherosclerosis is a complex and multifac torial process involving the influences of lipid deposition, blood pressure, rheologic forces, carbohydrate tolerance, and thrombogenic factors (fibrinogen and platelets). Atherosclerosis is markedly accelerated by other risk factors, more so in the presence of concomitant hypercholes terolemia, hypertension, diabetes, upper body obesity. Furthermore, the risk associated with anyone of these risk factors varies widely depending on level of the associated atherogenic risk factors.

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.

"Neuropeptides and Stress" presents a comprehensive survey by leading pioneers in the field of the knowledge and concepts implicating neuropeptides in the regulations of responses to stress. Topics covered include: recent advances on the regulation and modulation of the behavioral, endocrine, autonomic, gastrointestinal, immune and analgesic responses to stress by neuropeptides. Neuroanatomical and biological data are considered. Special emphasis is given to corticotropin-releasing factor (CRF) and opioid peptides.

A growing majority of women in the western hemisphere have been delaying initiation of childbearing to later in life. Consequently, more than ever before, women in their late 30s to early 40s are attempting their first pregnancy. Since the incidence of most cancers increases with age, delayed childbearing results in more female cancer survivors interested in fertility preservation." Fertility Preservation in Females: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this unique and practical reference guide for reproductive endocrinologists, gynecologists, embryologists, reproductive scientists, and oncologists provides strategies for fertility preservation in women, using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms."

In a state-of-the-art synthesis of basic science and clinical practice, Roy Smith and a distinguished panel of researchers and clinicians review GH regulation and its action at the molecular level, and describe the basis for GH deficiency and the use of GH as therapy in a variety of clinical situations. The clinical presentation moves beyond the treatment of GH-deficient children to include the genetics of GH-deficiency, GH-deficiency in adults, osteoporosis, Syndrome X, sleep quality, GH in AIDS patients, GHRH in clinical studies. Timely and innovative, Human Growth Hormone: Research and Clinical Practice will benefit both basic and clinical researchers, as well as those clinical endocrinologists who want to use growth hormone not only in treating children, but also in treating adult disorders, including those associated with metabolic disease.

The past two decades have seen steady progress in our understanding of the pathogenesis of atherosclerosis. The role of low density lipoprotein (LOL) increase and of LOL receptor deficiency or malfunctions in familial hypercholesterolemia has been largely enlightened by the works of Brown and Goldstein. These authors postulated also that modification of LOL to a form recognized by the scavenger or acetyl-LOL receptor may be required for lipid loading of macrophage-derived foam cells in the lesions. A growing body of evidence suggests that oxidative modification of LOL could enhance its atherogenicity by its implication as a factor in the generation of foam cells. Thus, if the role of LOL in the pathogenesis of hypercholesterolemia was well established a great deal of information appears currently on new approaches such as the mechanisms leading to the accumulation of foam cells, the impact of LOL structural alterations, notably oxidation and the role of gene mutations of apolipoprotein Band/or LOL receptor The opening topic is devoted to these new avenues outlined in the field of hypercholesterolemia. The first part concerns the genetic aspects of atherosclerosis: mainly the genetics of apo 1 ipoprote ins , their transcriptional regulation, the amino acid mutations of the apo B gene and of the LOL receptor gene, the structural domains and the acylation sites of apoprotein B.

The present volume is the results of 6 years' work by our team, during which time 2300 CT scans of the pituitary region were carried out. This was made possible by the close collaboration between physicians and technicians in our neuroradiological department, as well as by numerous corresponding physi cians. We wish to express our gratitude for their confidence and our sincere thanks to our colleagues at Besan90n, Dijon, Grenoble, Lyon, Montpellier, and Strasbourg. Furthermore, we especially wish to thank the patients who willingly accepted the difficult requirements of these studies. We are grateful to the technicians at the Neuroradiology Department of the Centre Hospitalier et U niversitaire de Besan90n, who have perfected the methodology so as to meet the ever increasing imperatives for precise anatomical mapping of the pituitary gland and the surrounding region; without their efforts, this book would never have been possible. Finally, we wish to express our thanks to the medical photographer of our group, as well as the secretarial staff for their contribution to the successful production of this work. We thank Labora toires Guerbet and General Electric for their excellent assistance, and Springer Verlag for their care and competence in the production of this book. In writing Computed Tomography of the Pituitary Gland, we have sought to develop morphological study of the pituitary gland to a degree of reliability comparable to that of laboratory findings in endocrine disorders.

In Cushing's Disease, leading authorities in the field offer a thorough review of the pathogenesis, diagnostic algorithm and treatment options for this complex disease. Beginning with a fascinating history of Cushing's disease that outlines its historical significance to both endocrinology and neurosurgery, the book goes onto to cover the full range of important issues, including the molecular pathogenesis of Cushing's, anatomic pathology, the diagnosis of Cushing's syndrome, the differential of pseudo-Cushing's syndromes, hypercortisolemia, surgical removal of the corticotroph adenoma, post-operative management and assessment of remission, radiotherapeutic options, and the exciting developments in medical therapy. In addition, the book also addresses Cushing's disease in the pediatric population, given that its clinical manifestations and impact on growth can be severe; silent corticotroph adenomas as a distinct clinical entity; diagnosis and management of Cushing's disease during pregnancy, bilateral adrenalectomy, and, finally, the long-term psychological manifestations of hypercortisolemia. Comprehensive and an invaluable addition the literature, Cushing's Disease is an essential reference for enhancing diagnosis and treatment of this debilitating disorder.

It is unclear, and really no longer relevant, whether the information explosion that we now contend with has been fostered by the growth of specialization and subspecialization in medicine, or vice versa. What is clear is that the two are mutually supportive and constitute what would be in endocrine parlance a short-loop positive feedback system. As a result, for most areas of medicine, even the subspecialist in that area has a problem in maintaining currency, the more general specialist has substan tial difficulty in doing so, and the generalist is tempted to abandon the effort altogether. Nevertheless, for all, both the internal pressures of conscience and self-esteem and the external pressures generated by peer review, recertifi cation, and subspecialty boards create the need for continuous self-educa tion. We are, therefore, in an era in which the means of dissemination of new information deserves as much creative attention as does its acquisition.

During the last ten years, the diagnostic approach to disorders of bone and mineral metabolism has benefited considerably from the development of radioimmunoassay and competitive protein- binding techniques for measurements of circulating parathyroid hormone, calcitonin, and biologically active vitamin D me- tabolites. Accumulated experiences with radiogrametrical and densinometric methods of quantitating appendicular bone mass now facilitate the detection of changes in bone mineral content heretofore unrecognized by routine roentgenographic vertebral analysis. During this same decade, the diagnosis of metabolic bone disease and the skeletal response to remedial therapeutic ma- neuvers have also been facilitated by the routine application of the bone biopsy. Improvements in tinctorial techniques, stan- dardization in methodology essential for adequate preparation of thin undecalcified specimens, and the incorporation of tetracy- cline bone formation or mineralization "markers" should now herald the "routine" use of this diagnostic procedure. Moreover, the compilation and ready availability of reference morphometric data, spanning the prepubescent years charac- terized by skeletal growth and remodeling and the later senes- cent period during which bone loss normally proceeds in an un- 7 8 FOREWORD relenting fashion, allow adequate differentiation between normal age-sex-related changes in skeletal turnover attendant on skeletal maturation and aging and acquired or inherited de- rangements in bone metabolism.

During the last two decades, progress in steroid hormone research has resulted in the development of new approaches to contraception as well as diagnosis and treatment of endocrine disorders and cancers. Although significant advances have been made in the purification, characterization, immunochemistry and molecular biology of steroid receptors, the precise molecular mechanism of steroid hormone action has remained obscure. This book captures the detailed presentations made at the first conference on Steroid Receptors in Health and Disease held at Meadow Brook Hall, Oakland University in the fall of 1987. The purpose of this international con ference was to facilitate scientific exchange toward a better understand ing of the mode of action of steroid hormones. The scientific sessions consisted of poster presentations and state-of-the-art lectures, the latter of which make up this volume. The first chapter is meant to provide the reader with a more general background of the topics covered in the book, as well as to discuss certain theme-related issues that are either not yet well-established or accepted or are in the stage of infancy. It is hoped that this volume will serve as a useful treatise for students and investigators interested in basic and clinical aspects of biological regulation by steroid hormones. A task of this magnitude could not have been undertaken without the encouragement, advice and continued generous assistance of the members of the scientific committee. I am gratefully indebted to Drs."

A cutting-edge review of how derangements in the hormonal and growth factor mechanisms controlling normal mammary development lead to breast cancer. Drawing on the multidisciplinary expertise of leading authorities, the book highlights the roles of oncogenes and tumor suppressor genes, spelling out the importance of autocrine/paracrine loops (e.g., stromal epithelial interactions) in supporting breast cancer cell proliferation and the progression to hormone independence. The book's many prominent contributors also illuminate significant recent advances in the biochemistry and physiology of hormone receptors and review the state-of -the-art in the endocrine therapy of breast cancer. Endocrinology of Breast Cancer provides a unique integrated overview of the most significant basic and clinical developments concerning the hormonal aspects of breast cancer.

In the words of Disraeli, "To be conscious that you are ignorant of the facts is a great step to knowledge. " For most of us, the conscious awareness of relative ignorance is an uncomfortable aspect of daily life. New data appear in such inexorable profusion that the necessity for continuous retooling has joined death and taxes as an inescapable component of our destinies. Perhaps it is this "consciousness of ignorance" that accounts for the success of the preceding volumes of this new series. The Year in Metabolism and The Year in Endocrinology series were introduced with the avowed intention of "providing an efficient and enjoyable bridge between those who are creating new knowledge at the bedside and the professional consciousness of those for whom such knowledge is ultimately intended. " That objective seems particularly appropriate at a time when the award of the 1977 Nobel Prize in Medicine or Physiology to Guillemin, Schally, and Yalow has served to emphasize the epoch-making advances that have characterized the recent course of endocrinology and me bolism. For the 1977 volume of The Year in Metabolism, the previous formula has been preserved. The same internationally recognized authorities again have contributed commentaries about the progress in their areas of expertise. They have been joined by Drs. Jack W. Coburn, David L. Hartenbower, and Charles R. Kleeman, who have provided a new section on Divalent Ion Metabolism.

This fifth edition of Autonomic Failure covers the many recent advances made in our understanding of the autonomic nervous system. There are numerous new chapters and extensive revisions of all other contributions. This book makes diagnosis increasingly precise by fully evaluating the underlying anatomical and functional deficits, thereby allowing more effective treatment. This new edition continues to provide a rational guide to aid in the recognition and management of autonomic disorders for practitioners from a variety of fields, including neurology, cardiology, geriatric medicine, diabetology and internal medicine.

The central nervous system controls vital functions by ef?ciently coordinating peripheral and central cascades of signals and networks in an orchestrated manner. Historically, the brain was considered to be insulin independent. These earlier views have been challenged by ?ndings demonstrating that insulin exerts multiple actions in the brain, regulating vital biological processes such as life span, neuronal survival, cognition, reproduction, feeding behavior, energy balance, and glucose and fat metabolism, and that inef?cient central action of insulin contributes to the development of severe pathologies (Banks et al. 2000; Gerozissis 2003, 2004, 2008; Lustman and Clouse 2005; Okamoto et al. 2001; Park 2002; Perrin et al. 2004; Pocai et al. 2005; Reger et al. 2008; Schwartz and Porte, 2005; Schubert et al. 2004; van der Heide et al. 2005; Woods et al. 1979; Wrighten et al. 2008). Insulin and speci?c insulin receptors are widely distributed in the networks of the central nervous system related mainly to feeding or cognition (Baskin et al. 1983; Bruning et al. 2000; Gerozissis 2003, 2008; Havrankova et al. 1978a, b; Schechter et al. 1996; Schulingkamp et al. 2000; Schwartz et al. 1992; Zhao et al. 2004). Insulin receptors located in the synapses of neurons and in astrocytes are present in high concentrations in the cerebral cortex, olfactory bulb, hippocampus, amygdala, cerebellum and hypothalamus (Abbott et al., 1999; Havrankova et al.

Thyroid function tests are utilized by essentially all medical practitioners, across every clinical setting, in patients from newborns to the elderly. They are the most frequently measured endocrine tests. The sensitive thyrotropin (TSH) assay reflects thyroid hormone feedback to the pituitary, and is diagnostic of both thyroid h- mone excess as well as deficiency. The log-linear relationship between serum TSH and thyroxine concentrations means that small changes in serum thyroxine are amplified by changes in serum TSH. The availability of the sensitive TSH assay in essentially all clinical laboratories has improved and simplified the assessment of thyroid function for the diagnosis of thyroid disease and to monitor treatment. Serum free thyroxine and thyrotropin concentrations, as well as other thyroid tests, can be measured utilizing an automated immunoassay platform that provides rapid and accurate results. This simplified approach to thyroid assessment, often requ- ing only a serum TSH measurement, and rapid availability of the thyroid function tests results, has expanded the scope of thyroid testing and clinicians ordering and interpretingth yroid tests. There remain, however, many challenges in selecting the appropriate thyroid function test to order, the correct interpretation of results, and applying these results to the diagnosis and management of thyroid diseases. It is especially important to be aware of limitations of thyroid function tests, as well as special clinical c- cumstances that can influence thyroid function measurements. The serum TSH concentration, for example, may not accurately reflect thyroid status in many si- ations including after prolonged hyperthyroidism when serum TSH remains s- pressed for months, in the presence of hypothalamic or pituitary disease, or due to a number of interfering medications. The serum free thyroxine, measured by the analog method, is not accurate with high or low serum binding proteins and d- ing pregnancy. Hospitalized patients often have thyroid function test abnormalities that are transient and return to normal after recovery from the acute illness. Iodine excessand deficiency candramatically influence thyroid function tests. Significant insights have been gained into the regulation of thyroid hormone synthesis and especially the role of thyroid hormone metabolism in supplying t- sues locally with an adequate supply of thyroid hormone. In a number of instances, these factors influence the selection and interpretation of thyroid function tests. Polymorphisms, common sequence variations, in genes of components that regulate thyroid function and thyroid hormone action may also contribute to variability in thyroid function tests in a population. v vi Preface This volume draws on an outstanding international panel of experts in thyroid function tests and thyroid function assessment. They represent clinicians, clinical researchers, and basic science researchers, all with a focus on some aspect of the assessment of thyroid function. The chapters all provide a clinical perspective, but are informed by themost recent scientific advancements. The first section of the book (Chaps. 1-3) presents the most recent advances in thyroid physiology, a review of genetic influences on thyroid function tests, and a discussion on the influence of iodine on thyroid function. In Chap. 1, Drs. Huang and de Castro Neves describe thyroid hormone metabolism, emphasizing the key role of thyroid hormone activation and inactivation in thyroid hormone action. Dr. Visser is a world leader in studies of thyroid metabolism and genetic influences on thyroid function. In Chap. 2, Dr. Visser and his colleagues, Drs. van der Deure, Medici, and Peeters, provide a clear view of this important and r- idly expanding field. The population variation in the TSH "set point" (relationship between serum TSH and thyroxine in an individual), for example, is thought to be genetically determined, and influences the evaluation of thyroid function and thyroid function targets for treatment of thyroid disease. Dr. Zimmerman, an int- nationally recognized expert in iodine, and his colleague, Dr. Andersson, provide in Chap. 3 an in-depth treatment of the most significant influence on thyroid function throughout the world-iodine intake. The influence of iodine deficiency and excess on individual thyroid function is discussed, as well as the population effects on t- roid diseases and especially fetal and neonatalde velopment. The basics of thyroid function measurements, approaches, limitations, and cl- ical applications are described for the major categories of thyroid function tests (Chaps. 4-7). The authors of these chapters are innovators in the field, strongly id- tified with the origination or significant refinement of the core tests utilized in t- roid assessment. In Chap. 4, Dr. Hershman describes the measurement of TSH, the clinical application and utilization. This remains the cornerstone of thyroid testing, but must be interpreted with an understanding of the dynamics of thyroid regulation. An active controversy in thyroid measurement involves the appropriate use of serum thyroxine measurements and especially the value of the analog free thyroxine me- urement, the most commonly used thyroxine assay. In Chap. 5, Dr. Stockigt p- vides a detailed assessment of thyroxine and triiodothyronine measurements and a clear message for their use and limitations. The most common etiology of thyroid disease is autoimmune, and the appropriate use of thyroid autoantibody measu- ments remains confusing to many clinicians. In Chap. 6, Dr. Weetman and his c- league, Dr. Ajjan, clearly describe the range of thyroid autoantibody tests and how they should be utilized clinically. Thyroglobulin measurement is the key tumor marker to follow thyroid cancer patients and Dr. Spencer and her colleague, Ivana Petrovic, describe the essential features of this measurement in Chap. 7. It is ess- tial that clinicians using thyroglobulin measurements to monitor thyroid cancer are aware of the performance of the assay being used and the factors that can interfere with the measurement. Application of thyroid function testing to the key clinical settings is discussed by expert clinicians and clinical researchers in Chaps.8-13. The appropriate selec- Preface vii tion of thyroid function tests in the diagnosis and monitoring of thyroid disease in the ambulatory setting is discussed by Drs. Farwell and Leung in Chap. 8. This is the most common setting for thyroid function test measurement and a rational approach is described. Specific issues of thyroid function in infants and children are discussed in Chap. 9 by Drs. LaFranchi and Balogh. Screening for thyroid disease among newborns has been a highly effective approach to prevent mental retar- tion. The assessment of thyroid function in newborns, especially premature infants, is challenging as are the interpretation of thyroid function tests in infancy through childhood. Illness has a significant impact on thyroid function tests and assessment in this group is described by Drs. LoPresti and Patil in Chap. 10. A logical approach to these patients is provided as are ways to identify those patients with thyroid disease that need to be treated. Assessment of thyroid function in pregnancy is ch- lenging and is being increasing recognized as a crucial time to normalize maternal thyroid status. Adverse outcome for mother and her child can result from thyroid hormone deficiency or excess. In Chap.11, Drs. Lazarus, Soldin, and Evans ca- fully describe the use and limitations of thyroid tests in pregnancy and provide an approach to testing and monitoring thyroid function. The incidence of autoimmune thyroid disease increases significantly with age and in Chap. 12 Dr. Samuels p- vides a clear approach to the assessment of thyroid status in the elderly and interp- tation of thyroid studies. The influence of drugs on thyroid function testing remains a major clinical issue with recognition of an ever increasing list of medications that influence thyroid function and thyroid testing. In Chap. 13, Drs. Pearce and An- thakrishnan comprehensively describe these medications with a special emphasis on their mechanism of action and on iodine-containing medications. I am most grateful to my colleagues for their enthusiasm and willingness to p- vide such outstanding contributions to this book. The editorial team at Springer is excellent and has been highly supportive and effective. My special thanks to E- tor Laura Walsh, Associate Editor Dianne Wuori, Editorial Assistant Stacy Lazar, Senior Production Editor Jenny Wolkowicki and Crest Premedia Solutions for final production.

Most of us spend at least two-thirds of our lives either sitting or standing. It is somewhat surprising, therefore, to find not a single book devoted to disorders caused by derangements of the normal physiological adjustments to changes in posture. In fact, until very recently, medical students have not even been advised to measure the blood pressure and heart rate in the upright posture as part of the routine physical examination. Although Bradbury and Eggleston first described orthostatic hypotension as a consequence of autonomic insufficiency in 1925, interest in orthostatic disorders has been slow to develop in the subsequent years. It is well known that the change from recumbency to the standing posture stimulates neurological, endocrine, and cardiovascular adjustments that ensure maintenance of a normal circulation despite the effects of gravitational forces. The mechanisms of these physiological responses to orthostasis have been stud ied by many investigators. Some of the defects to which antigravitational com pensatory mechanisms are subject, such as postural hypotension resulting from autonomic failure, have been studied intensively and have become part of the general knowledge of most medical practitioners. Other orthostatic disorders such as various other postural abnormalities of blood pressure control, and orthostatic edema-have received far less attention and have been unable to compete with the more dramatic and life-threatening ailments of humankind for a place in our standard medical texts. These disorders often give rise to distressing symptoms and may lead to severe impairment of health.